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https://www.readbyqxmd.com/read/28666189/oral-metronomic-topotecan-sensitizes-crizotinib-antitumor-activity-in-alk-f1174l-drug-resistant-neuroblastoma-preclinical-models
#1
Libo Zhang, Bing Wu, Sylvain Baruchel
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients. We aimed to overcome crizotinib resistance by combining with the MEK inhibitor trametinib or low-dose metronomic (LDM) topotecan in preclinical neuroblastoma models. METHODS: We selected a panel of neuroblastoma cell lines carrying various ALK genetic aberrations to assess the therapeutic efficacy on cell proliferation in vitro...
June 27, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28617871/hypoxia-inducible-factor-1%C3%AE-plays-roles-in-epstein-barr-virus-s-natural-life-cycle-and-tumorigenesis-by-inducing-lytic-infection-through-direct-binding-to-the-immediate-early-bzlf1-gene-promoter
#2
Richard J Kraus, Xianming Yu, Blue-Leaf A Cordes, Saraniya Sathiamoorthi, Tawin Iempridee, Dhananjay M Nawandar, Shidong Ma, James C Romero-Masters, Kyle G McChesney, Zhen Lin, Kathleen R Makielski, Denis L Lee, Paul F Lambert, Eric C Johannsen, Shannon C Kenney, Janet E Mertz
When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas (HIF-αs). We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV). Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28592433/bifurcated-bach2-control-coordinates-mantle-cell-lymphoma-survival-and-dispersal-during-hypoxia
#3
Han Zhang, Zheng Chen, Roberto N Miranda, L Jeffrey Medeiros, Nami McCarty
BACH2, a B cell-specific transcription factor, plays a critical role in oxidative stress-mediated drug resistance in mantle cell lymphoma (MCL); however, the biological functions of BACH2 and its regulation of B cell malignancies in chronic hypoxic microenvironment are never studied. Here, we found that silencing BACH2 led to not only increased tumor formation and colony formation but also increased tumor dispersal to spleen and bone marrow. Decreased BACH2 levels in the patients were also correlated to the bone marrow and gastrointestinal dispersal of MCL and blastoid subtypes of MCL...
June 7, 2017: Blood
https://www.readbyqxmd.com/read/28586054/propofol-reduces-hypoxia%C3%A2-induced-autophagic-cell-death-through-downregulating-hif-1%C3%AE-in-alveolar-epithelial-type-ii-cells-of-rats
#4
Hui-Jie Ning, Hong-Bin Yuan, Hai-Tao Xu, Xing-Ying He
Propofol (2,6‑diisopropylphenol) exerts protective effects on alveolar epithelial type II (ATII) cells, partly through attenuating hypoxia‑induced apoptosis. Autophagy is involved in the activation of apoptosis. Therefore, the present study investigated the modulating effect of propofol against autophagy in ATII cells under hypoxia. Western blot analysis was performed to detect the protein expression of the autophagy molecular marker, microtubule‑associated protein 1 light chain 3 (LC3)‑II, under various conditions...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28489881/hypoxia-activated-prodrug-th-302-decreased-survival-rate-of-canine-lymphoma-cells-under-hypoxic-condition
#5
Hiroki Yamazaki, Yu-Chang Lai, Morihiro Tateno, Asuka Setoguchi, Yuko Goto-Koshino, Yasuyuki Endo, Munekazu Nakaichi, Hajime Tsujimoto, Naoki Miura
We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells...
2017: PloS One
https://www.readbyqxmd.com/read/28433571/antitumor-and-chemosensitizing-action-of-3-bromopyruvate-implication-of-deregulated-metabolism
#6
Saveg Yadav, Shrish Kumar Pandey, Ajay Kumar, Praveen Kumar Kujur, Rana Pratap Singh, Sukh Mahendra Singh
3-Bromopyruvate (3-BP), brominated derivative of pyruvate, possesses strong antitumor potential, owing to its ability to inhibit multiple target molecules crucial for survival of neoplastic cells. Although, 3-BP displays cytotoxicity against a wide variety of tumors, there is no report with respect to malignancies of thymic origin. Therefore, we investigated its antineoplastic action in vitro against tumor cells of a murine transplantable lymphoma of thymoma origin, designated as Dalton's lymphoma (DL). 3-BP treatment of tumor cells inhibited metabolism and survival with augmented induction of apoptosis and necrosis...
May 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28426671/effect-of-mitochondrially-targeted-carboxy-proxyl-nitroxide-on-akt-mediated-survival-in-daudi-cells-significance-of-a-dual-mode-of-action
#7
Gokul Variar, Tarun Pant, Apoorva Singh, Abinaya Ravichandran, Sushant Swami, Balaraman Kalyanaraman, Anuradha Dhanasekaran
Vicious cycles of mutations and reactive oxygen species (ROS) generation contribute to cancer progression. The use of antioxidants to inhibit ROS generation promotes cytostasis by affecting the mutation cycle and ROS-dependent survival signaling. However, cancer cells select mutations to elevate ROS albeit maintaining mitochondrial hyperpolarization (Δψm), even under hypoxia. From this perspective, the use of drugs that disrupt both ROS generation and Δψm is a viable anticancer strategy. Hence, we studied the effects of mitochondrially targeted carboxy proxyl nitroxide (Mito-CP) and a control ten carbon TPP moiety (Dec-TPP+) in the human Burkitt lymphoma cell line (Daudi) and normal peripheral blood mononuclear cells under hypoxia and normoxia...
2017: PloS One
https://www.readbyqxmd.com/read/28259980/genistein-decreases-a549-cell-viability-via-inhibition-of-the-pi3k-akt-hif%C3%A2-1%C3%AE-vegf-and-nf%C3%A2-%C3%AE%C2%BAb-cox%C3%A2-2-signaling-pathways
#8
Juan Zhang, Hongzheng Su, Qingfeng Li, Jing Li, Qianfeng Zhao
Genistein is an important chemopreventive agent against atherosclerosis and cancer. However, whether genistein is effective in the treatment of lung cancer, and its underlying mechanism, remains to be determined. The present study demonstrated that genistein treatment of A549 lung cancer cells decreased viability in a dose‑ and time‑dependent manner, and induced apoptosis. Additionally, A549 cells exhibited significantly increased reactive oxygen species formation and cytochrome‑c leakage, and activated caspase‑3, B‑cell lymphoma 2‑associated X protein and apoptosis inducing factor expression levels, which are involved in the mitochondrial apoptosis pathway...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28123543/increased-chemosensitivity-and-radiosensitivity-of-human-breast-cancer-cell-lines-treated-with-novel-functionalized-single-walled-carbon-nanotubes
#9
Yijun Jia, Ziyi Weng, Chuanying Wang, Mingjie Zhu, Yunshu Lu, Longlong Ding, Yongkun Wang, Xianhua Cheng, Qing Lin, Kejin Wu
Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28104392/scutellarein-antagonizes-the-tumorigenesis-by-modulating-cytokine-vegf-mediated-neoangiogenesis-and-dff-40-actuated-nucleosomal-degradation
#10
Prabhu Thirusangu, V Vigneshwaran, B R Vijay Avin, H Rakesh, H M Vikas, B T Prabhakar
Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation...
February 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27866977/the-anti-hyperplasia-anti-oxidative-and-anti-inflammatory-properties-of-qing-ye-dan-and-swertiamarin-in-testosterone-induced-benign-prostatic-hyperplasia-in-rats
#11
Xinying Wu, Ye Gu, Lun Li
Qing Ye Dan (QYD) is the whole plant of Swertia mileensis and used in Chinese folk medicine for the treatment of prostatitis, benign prostatic hyperplasia (BPH) and so on. This study was to investigate the effects of QYD and its main component swertiamarin on BPH induced by testosterone in rats. The prostatic expressions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (βFGF) and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry assay...
January 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27765090/-effects-of-severe-hypoxia-and-low-concentration-of-serum-protein-on-the-function-of-human-hypertrophic-scar-fibroblasts
#12
J Y Dong, F Song, Y K Liu, X Q Wang
Objective: To simulate the environmental factors during the process of formation and evolution of hypertrophic scar, so as to explore the effects of moderate and severe hypoxia and low concentration of serum protein on the function of human hypertrophic scar fibroblasts (HSFs). Methods: Human HSFs were routinely cultured. Cells of the 3rd to the 6th passage were divided into 10.0% oxygen+ 10.0% fetal calf serum (FCS), 5.0% oxygen+ 5.0% FCS, and 0.5% oxygen+ 0.5% FCS groups according to the random number table...
October 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27748274/level-of-pax5-in-differential-diagnosis-of-non-hodgkin-s-lymphoma
#13
Brij Bharti, Sachin Shukla, Ratnakar Tripathi, Suman Mishra, Mohan Kumar, Manoj Pandey, Rajnikant Mishra
BACKGROUND & OBJECTIVES: The PAX5, a paired box transcription factor and B-cell activator protein (BSAP), activates B-cell commitment genes and represses non-B-cell lineage genes. About 14 transcript variants of PAX5 have been observed in human. Any alteration in its expression pattern leads to lymphogenesis or associated diseases and carcinogenesis in non-lymphoid tissues. Its mechanisms of function in pathophysiology of non-Hodgkin's lymphoma (NHL) are unclear. This study was intended to explore influence of PAX5 in cascade of NHL pathogenesis and diagnosis...
May 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27543313/functional-implications-of-the-spectrum-of-bcl2-mutations-in-lymphoma
#14
REVIEW
Khushboo Singh, James M Briggs
Mutations in the translocated BCL2 gene are often detected in diffuse large B-cell lymphomas (DLBCLs), indicating both their significance and pervasiveness. Large series genome sequencing of more than 200 DLBCLs has identified frequent BCL2 mutations clustered in the exons coding for the BH4 domain and the folded loop domain (FLD) of the protein. However, BCL2 mutations are mostly contemplated to represent bystander events with negligible functional impact on the pathogenesis of DLBCL. BCL2 arbitrates apoptosis through a classic interaction between its hydrophobic groove forming BH1-3 domains and the BH3 domain of pro-apoptotic members of the BCL2 family...
July 2016: Mutation Research. Reviews in Mutation Research
https://www.readbyqxmd.com/read/27413173/bortezomib-alleviates-experimental-pulmonary-hypertension-by-regulating-intracellular-calcium-homeostasis-in-pasmcs
#15
Jun Zhang, Wenju Lu, Yuqin Chen, Qian Jiang, Kai Yang, Meichan Li, Ziyi Wang, Xin Duan, Lei Xu, Haiyang Tang, Dejun Sun, Jian Wang
The ubiquitin-proteasome system is considered to be the key regulator of protein degradation. Bortezomib (BTZ) is the first proteasome inhibitor approved by the US Food and Drug Administration for treatment of relapsed multiple myeloma and mantle cell lymphoma. Recently, BTZ treatment was reported to inhibit right ventricular hypertrophy and vascular remodeling in hypoxia-exposed and monocrotaline-injected rats. However, the underlying mechanisms remain poorly understood. We previously confirmed that hypoxia-elevated basal intracellular Ca(2+) concentration ([Ca(2+)]i) and store-operated Ca(2+) entry (SOCE) in pulmonary artery smooth muscle cells (PASMCs) are involved in pulmonary vascular remodeling...
September 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27297969/alterations-in-cellular-metabolism-modulate-cd1d-mediated-nkt-cell-responses
#16
Tonya J Webb, Gregory B Carey, James E East, Wenji Sun, Dominique R Bollino, Amy S Kimball, Randy R Brutkiewicz
Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells...
2016: Pathogens and Disease
https://www.readbyqxmd.com/read/27121066/hif-1%C3%AE-activates-hypoxia-induced-bcl-9-expression-in-human-colorectal-cancer-cells
#17
Zhen Tan, Quan Huang, Jia Zang, Shi-Feng Teng, Tian-Rui Chen, Hai-Feng Wei, Dian-Wen Song, Tie-Long Liu, Xing-Hai Yang, Chuan-Gang Fu, Zhi-Qian Hu, Wang Zhou, Wang-Jun Yan, Jian-Ru Xiao
B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/27107327/high-co-expression-of-pd-l1-and-hif-1%C3%AE-correlates-with-tumour-necrosis-in-pulmonary-pleomorphic-carcinoma
#18
Yih-Leong Chang, Ching-Yao Yang, Mong-Wei Lin, Chen-Tu Wu, Pan-Chyr Yang
BACKGROUND: Pulmonary pleomorphic carcinomas (PPCs) are uncommon malignant tumours characterised by an aggressive clinical course and poor survival. These neoplasms frequently exhibit marked confluent necrosis, in which hypoxia levels are extremely high, causing low responsiveness to chemotherapy and conferring basic resistance to anti-cancer drugs. Programmed death ligand 1 (PD-L1)-mediated immune escape may be an underlying source of resistance and a suitable target for specific therapy, but its role in PPCs is unclear...
June 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27102266/dual-time-point-fdg-pet-ct-and-fdg-uptake-and-related-enzymes-in-lymphadenopathies-preliminary-results
#19
Sofie Bæk Christlieb, Casper Nørgaard Strandholdt, Birgitte Brinkmann Olsen, Karen Juul Mylam, Thomas Stauffer Larsen, Anne Lerberg Nielsen, Max Rohde, Oke Gerke, Karen Ege Olsen, Michael Boe Møller, Bjarne Winther Kristensen, Niels Abildgaard, Abass Alavi, Poul Flemming Høilund-Carlsen
PURPOSE: The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with (18)F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed. METHODS: Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60 min and 180 min after FDG administration)...
September 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/26998070/downregulation-of-hif-1%C3%AE-inhibits-the-proliferation-and-invasion-of-non-small-cell-lung-cancer-nci-h157-cells
#20
Jialin Qian, Hao Bai, Zhiqiang Gao, Y U Dong, Jun Pei, Meili Ma, Baohui Han
Lung cancer, specifically non-small cell lung cancer (NSCLC), is the leading cause of cancer-associated mortality in the world. In previous years, almost no significant advancements have been made towards the molecular characterization of NSCLC, which highlights the requirement for novel target genes. Hypoxia inducible factor-1α (HIF-1α) is known to be essential in tumorigenesis, as it regulates the expression of numerous factors that are involved in angiogenesis, cellular proliferation and apoptosis. However, no direct association between HIF-1α and NSCLC treatment has previously been established...
March 2016: Oncology Letters
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